Synthesis of irbesartan

Abstract

Provided are a method of making irbesartan via a Suzuki coupling reaction and a novel intermediate, 2-butyl-3-(4′-bromobenzyl)-1,3-diazaspiro[4.4]non-1-ene-4-one, for such process. The novel process includes the step of reacting such intermediate with a protected imidazolephenylboronic acid.

1. A process for preparing irbesartan comprising the steps of:
 a) providing a solution of 2-butyl-3-[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl methyl]-1,3-diazaspiro[4.4]non-1-ene-4-one in a water miscible solvent; 
 b) acidifying the solution; 
 c) neutralizing the solution and separating the trityl alcohol, whereby a second solution is obtained 
 d) acidifying the second solution; 
 e) cooling the acidified second solution; and 
 f) recovering irbesartan. 
 
     
     
       2. The process of  claim 1 , wherein the water miscible solvent in step a is acetone. 
     
     
       3. The process of  claim 1 , wherein the second solution is cooled to about 0° C. to about (−4° C.).